Field of the Invention
The present invention relates to a near-infrared dye-bound transferrin, and a contrast agent for photoacoustic imaging, including the near-infrared dye-bound transferrin.
Description of the Related Art
A photoacoustic tomography (hereinafter, sometimes abbreviated as “PAT”) apparatus is known as one apparatus for visualizing information in a living body. In measurement using the PAT apparatus, an image in which the substance distribution in an object to be measured is computed can be obtained by measuring the intensity and the time of generation of a photoacoustic signal emitted from a substance (optical absorber) that absorbs light in the object to be measured, in irradiation of the object to be measured with light.
For the optical absorber, any substance can be here used as long as the substance absorbs light and emits an acoustic wave in a living body. For example, a blood vessel or a malignant tumor in a human body can be adopted for the optical absorber. Besides, molecules of indocyanine green (hereinafter, sometimes abbreviated as “ICG”) and the like can also be administered into a body and utilized as a contrast agent. ICG well absorbs light in the near-infrared wavelength region, the light having a small influence in irradiation of a human body therewith and having a high permeability to a living body, and therefore can be suitably used as a contrast agent (sometimes abbreviated as a “photoacoustic contrast agent”) in the PAT apparatus. In the present description, ICG refers to a compound represented by a structure of the following formula.

Herein, the counter ion may not be Na+, and any counter ion such as H+ or K− can be used.
It is known that, however, ICG has a very short half-life of about several minutes in blood.
NPL 1 (Photochemistry and Photobiology, 72, 234-241 (2000)) and NPL 2 (Molecular Imaging, 6, 85-95 (2007)) each disclose a compound in which an organic dye that absorbs light in the near-infrared wavelength region (hereinafter, sometimes abbreviated as “near-infrared dye”) is bound to transferrin that is a serum protein (sometimes abbreviated as “TF”). The near-infrared dye herein means an organic dye that absorbs light in the near-infrared wavelength region. The light in the near-infrared wavelength region herein means light at wavelengths of 600 nm to 1300 nm.
In the transferrin, to which the near-infrared dye is bound, disclosed in NPL 1, the number of dyes to be immobilized is 2.4/molecule and such a dye is a hydrophilic near-infrared dye having a plurality of sulfonic acids in the molecule. The compound is shown to serve as a fluorescent contrast agent of a tumor. According to the animal experimental results described in the present Literature, the fluorescent contrast between a tumor and a normal tissue (hereinafter, sometimes abbreviated as “imaging contrast”) is 1.9 at 24 hours after administration, and a further enhancement in the contrast is demanded for photoacoustic tumor imaging.
In the transferrin, to which an Alexa Fluor (registered trademark) 680 dye is bound, disclosed in NPL 2, the number of dyes to be immobilized is 2/molecule and such a dye is a hydrophilic near-infrared dye having a plurality of sulfonic acids in the molecule. As described later in Comparative Examples herein, the imaging contrast between a tumor and a normal tissue of the transferrin, to which the Alexa Fluor (registered trademark) 680 dye is bound, disclosed in is NPL 2, is 1.2 at 24 hours after administration, and a further enhancement in the contrast is demanded for photoacoustic tumor imaging.
Accordingly, a compound is demanded as a photoacoustic tumor contrast agent, which exhibits a high absorption coefficient in the near-infrared wavelength region, a high tumor accumulation property, a high tumor/blood ratio and a high imaging contrast.
The present invention has been made in view of such problems, and an object thereof is to provide a novel near-infrared dye-bound transferrin exhibiting a high absorption coefficient in the near-infrared wavelength region, a high tumor accumulation property, a high tumor/blood ratio and a high imaging contrast.